Several publications and patent documents are cited throughout the specification in order to describe the state of the art to which this invention pertains. Each of these citations is incorporated herein by reference as though set forth in full.
The biotechnology revolution has created vast new potential for pharmaceuticals, yet this potential remains unrealized due largely to problems in manufacturing. Biopharmaceuticals, which have greatly expanded targets for therapeutic intervention, now represent about 30% of the drugs in the development pipeline. However, the biopharmaceutical industry does not have the manufacturing infrastructure required to meet patient needs. In other words, discovery has far outpaced production. Drug development is associated with a variety of hurdles, including cycle-process changes, scale-up problems, and capacity shortages, all of which give rise to the need to repeat clinical trials thereby exhausting developers' money often before drugs can be approved for use.
Methods have been developed for producing biopharmaceuticals, particularly recombinant proteins such as enzymes and antibodies, in a variety of hosts, including bacteria, yeast, mammalian cell culture, and transgenic mammals and plants. However, each of these systems suffers from shortcomings. For example, proteins produced by bacterial fermentation fail to include biochemically important mammalian modifications. Mammalian cell culture cannot easily be scaled up to produce enough protein of commercial value and transgenic mammals are expensive and time consuming to produce and raise problems of public acceptance.
To be fully functional, most proteins require “post-translational modification” or further changes to overall structure and composition. The most common change involves a process called glycosylation, an enzyme-mediated addition of specific sugars to the protein backbone. Glycosylation is important for protein use in humans, as it can affect the efficacy, stability and often safety of a potential drug. The best known biotherapeutics are treatments for diabetes, Multiple sclerosis, Hodgkin's lymphoma, Crohn's disease, and various promising therapies for AIDS and cancer. Seven of the current top ten biopharmaceuticals (Procrit, Epogen, Intron A/Rebetron, Neupogen, Humulin, Avonex, Rituxan, Enbrel, Remicade, and Cerezyme) require glycosylation.
It would be desirable to produce recombinant proteins that have proper mammalian (e.g., human) glycosylation patterns, in insect cells. Such a process could provide the industry a flexible, low-capital-intensive, fast-turnaround, linearly scalable process for manufacturing authentic human-type glycoproteins for therapeutic applications.